Nitric oxide production and monoamine oxidase activity in cancer patients during interferon-alpha therapy.
Both increased and decreased nitric oxide (NO) synthesis have been reported in patients treated with interferon-alpha (IFN-alpha). Animal studies showed that IFN-alpha administration results in increased levels of biogenic amines, subsequent activation of monoamine oxidases (MAOs), and finally in a change in NO production due to the H(2)O(2) generated by MAOs. We examined the potential relationship between NO production in plasma and MAO-B activity in platelets of 43 cancer patients during 8 weeks of treatment with IFN-alpha. NO synthesis was quantitated by measuring both the ratio of citrulline and arginine (CIT/ARG-ratio) and total nitrite/nitrate (NOx) levels. Compared to baseline, MAO activity and NOx increased, while the CIT/ARG-ratio decreased. No associations were found between NOx, MAO and CIT/ARG-ratio. Only few associations were observed between changes in the biochemical parameters and changes in psychopathology induced by IFN-alpha, of which the association between changes in CIT and lassitude was the most consistent. The results suggest that peripheral NO production and MAO activity are unrelated to each other, and that peripheral changes in these biochemical parameters induced by IFN-alpha are unlikely to contribute to definite psychiatric disturbance.
Fekkes
Durk
D
Department of Neuroscience, Erasmus MC, Rotterdam, The Netherlands. d.fekkes@erasmusmc.nl
Van Gool
Arthur R
AR
Bannink
Marjolein
M
Sleijfer
Stefan
S
Kruit
Wim H J
WH
van der Holt
Bronno
B
Eggermont
Alexander M M
AM
Hengeveld
Michiel W
MW
Stoter
Gerrit
G
D000328:Adult; D000368:Aged; D001120:Arginine / Q000097:blood / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism; D002956:Citrulline / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000096:biosynthesis* / Q000097:blood; D009566:Nitrates / Q000097:blood / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000097:blood; D009573:Nitrites / Q000097:blood / Q000378:metabolism; D011446:Prospective Studies; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism
D016898:Interferon-alpha; D009566:Nitrates; D009573:Nitrites; D002956:Citrulline; D009569:Nitric Oxide; D001120:Arginine; D008995:Monoamine Oxidase